Outline

Objective: Hemangioblastomas are benign, highly vascularized tumors that can occur sporadically or as a component of von Hippel-Lindau disease, an autosomal dominant tumor syndrome. The cytological and anatomic origin of hemangioblastomas remains unknown.

Methods: To clarify the origin of these tumors we investigated the expression of hemangioblastic marker proteins in ten tumor samples. In addition we performed pathologic-anatomic autopsy studies on grossly normal appearing spinal cord of deceased VHL patients to clarify the anatomic origin of the tumors containing multiple microscopic lesions.

Results: We found that hemangioblastoma tumor cells express proteins (Scl, brachyury, Csf-1R, Gata-1, Flk-1 and Tie-2) that characterize embryonic hemangioblast progenitor cells and suggest that these cells represent the cytological equivalent of the tumor cells. Pathologic-anatomic studies revealed that hemangioblastomas arise at the dorsal root entry zone and progress from microscopic lesions to macroscopic tumors in a step-wise phenotypic pattern.

Conclusions: These findings can explain the highly selective distribution of hemangioblastomas through the CNS: During normal embryonic development, Scl-expressing cells are confined to those locations that give rise to the spinal cord, cerebellum and retina, which exactly matches the distribution of hemangioblastomas.